A comparison of four PET tracers for brain hypoxia mapping in a rodent model of stroke.

Abstract:

INTRODUCTION: Severe brain hypoxia in the territory of the occluded artery is a key feature of ischemic stroke. This region can be imaged using positron emission tomography (PET) and the standard hypoxia radiotracer (18)F-fluoromisonidazole ((18)F-FMISO). However, the utility of (18)F-FMISO is limited by its slow accumulation in the lesion. Therefore, this study investigated three hypoxia-sensitive radiotracers, namely the nitroimidazole (18)F-fluoroazomycin arabinoside ((18)F-FAZA) and two (64)Cu bis(thiosemicarbazone) complexes ((64)Cu-ATSM and (64)Cu-ATSE), expected to have improved pharmacokinetic profiles relative to (18)F-FMISO, in a rodent model of ischemic stroke. METHODS: In anaesthetised Wistar rats, the distal middle cerebral artery was permanently occluded by electrocoagulation, the radiotracers administered intravenously and animals PET scanned for up to 3hours, followed by T2-weighted magnetic resonance imaging to map the infarct. RESULTS: As expected, late and prominent (18)F-FMISO retention was observed despite lower tracer delivery into the affected region. Time-activity curves revealed that both (64)Cu-ATSM and (64)Cu-ATSE showed rapid entry and efflux from the brain, but did not show significant accumulation in the lesion. (18)F-FAZA showed limited brain penetration, and accumulation in the lesion was inconsistent, low and as slow as (18)F-FMISO. CONCLUSIONS: This study suggests further development of these radiotracers as hypoxia markers for ischemic stroke may not be warranted.